The venereal and congenital of infectious human retroviruses (RVs), including the Human Immunodeficiency Viruses (HIVs), has created an urgent need to understand the pathobiology of RVs in human reproductive tract tissues. Evidence from this laboratory and others is that reproductive tract cells of humans and mice express retroviruses (RVs) at significantly higher levels than somatic tissues. Endogenous virus expression has been well documented for mouse tissues and more recently detected in human tissues in this laboratory. In addition, recent studies in other laboratories of the tissue distribution of infectious RVs in mice inoculated as neonates have revealed high level expression of virus in male and female reproductive trac tissues. A notable exception to this was female tissues of the AKR in male and female reproductive tract tissues. A notable exception to this was female tissues of the AKR strain that express endogenous viral proteins were resistant to superinfection by exogenous virus. Thus, the possible consequences of endogenous RV expression by reproductive tract cells include resistance to HIV infection and cross- regulation of transcription in cells infected by HIV that also express endogenous RVs. Simultaneous expression of HIV and endogenous RVs could provide the opportunity for recombination events between the viral genomes. Although such recombinant viruses have not as yet been described, the possibility is an important one because it could yield viruses with increased pathogenicity and a wider host cell range for infection. An additional possibility in need of study is whether the offspring of HIV- infected parents are transgenic for HIV. It is important to understand whether or not HIV will be expressed as endogenous provirus in such transgenic individuals. The goals of this proposal are to provide information essential to begin to understand RV interaction and expression in human reproductive tract of infected adults express HIV; 2) characterize the endogenous RVs expressed in reproductive tract cells of normal and HIV-infected individuals; 3) determine which cells in the reproductive tracts of HIV-positive offspring are infected with virus. The results of these studies will provide background information necessary for a more complete understanding of the biology of retroviruses in the human reproductive tract. Such information is essential to designing modes of therapy and control of venereal and congenital transmission of HIV.